CORE--CELL BIOLOGY LABORATORY

核心--细胞生物学实验室

• 批准号: 6241647
• 负责人: Bertram Harold Lubin
• 金额: $ 26.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241647
• 关键词: adult human (21+); biomedical facility; biophysics; bone marrow transplantation; butyrates; cell adhesion; child (0-11); erythrocyte membrane; flow cytometry; human subject; hydroxyurea; membrane structure; respiratory disorder; sickle cell anemia

There is a great deal of clinical variability in patients with sickle cell disease. Although alpha thalassemia and fetal hemoglobin levels have been identified as important factors in regard to clinical severity, the clinical course in many patients can not be explained based upon these two parameters and additional factors must be sought. Our hypothesis is that careful evaluation of cellular and membrane parameters such as deformability, density profile and adherence to endothelial cells in patients who are simultaneously being evaluated for clinical problems related to sickle cell disease, may provide new insights into the relationship between membrane or cellular abnormalities and the pathophysiology of sickle cell disease. We have included this core facility in our center application so that we can add specific biophysical measurements to our clinical and basic research projects and enhance the information we will derive from these projects. An established cell biology-biophysical facility will be used to investigate cell deformability by ektacytometry of ghosts and intact red blood cells, density profiles on a prototype Technicon H-1 and red cell-endothelial cell adherence using a newly developed, clinically applicable method. When significant abnormalities are detected in either deformability or adherence, further evaluation of these cells, or the plasma in which these cells were suspended, will be undertaken. For these measurements, a micropipette assay will be used to characterize the defects in cell deformation or to characterize the abnormalities in adherence and analysis will be done on whole blood as well as density fractionated red cells. The clinical projects which this core facility will be most helpful in are 1.) drug trials with hydroxyurea or butyric acid in children and adults, 2.) acute chest syndrome patients at baseline and throughout their clinical course, 3.) patients in the central nervous system study, 4.) children followed during the first three years of life, 5.) patients who have severe clinical manifestations compared to patients who have mild disease, 6.) and patients who have undergone bone marrow transplantation. The studies in patients treated with hydroxyurea will be of particular interest as their red cells are known to have a dramatic increase in MCV and careful characterization of the membrane/cellular properties of these cells has not been performed. By comparing the results we obtain in the cell biology core to the clinical course of patients under study, we hope to establish the relative importance of these cellular changes to the pathophysiology of sickle cell disease.

镰状患者的临床变异性很大 细胞疾病 虽然α地中海贫血和胎儿血红蛋白水平 已被确定为临床严重程度的重要因素， 许多患者的临床病程无法根据 必须寻求这两个参数和其他因素。 我们 假设是仔细评估细胞和膜参数 例如变形性、密度分布和对内皮细胞粘附性 同时接受临床问题评估的患者 与镰状细胞病有关，可能会提供新的见解 细胞膜或细胞异常与 镰状细胞病的病理生理学 我们把这个核心 在我们的中心应用程序中，我们可以添加特定的 生物物理测量我们的临床和基础研究项目， 加强我们从这些项目中获得的信息。 一个 将使用已建立的细胞生物学-生物物理学设施来研究 通过血影和完整红细胞的ektacytometry测定的细胞变形性， 原型Technicon H-1和红细胞内皮细胞上的密度分布 细胞粘附使用新开发的，临床上适用的方法。 当检测到变形性或 粘附，进一步评价这些细胞，或血浆中， 这些细胞被暂停，将进行。 对于这些测量， 将使用微量移液管测定来表征细胞中的缺陷。 变形或表征粘附异常， 将对全血以及密度分级红细胞进行分析 细胞这个核心设施将是最重要的临床项目， 有帮助1）药物试验与羟基脲或丁酸在 儿童和成人（2）基线时的急性胸部综合征患者， 在整个临床过程中，3.）中枢神经系统患者 系统研究，4.）孩子们在出生后的头三年， 5.）与患者相比，临床表现严重的患者 有轻微疾病的人，6。接受骨髓移植的病人 移植 在接受羟基脲治疗的患者中进行的研究将 特别令人感兴趣的是，已知他们的红细胞具有显著的 MCV的增加和膜/细胞的仔细表征 这些单元格的属性尚未执行。 通过比较 我们在临床过程的细胞生物学核心中获得的结果 研究中的患者，我们希望建立相对重要性， 这些细胞变化与镰状细胞病的病理生理学有关。